This proposal requests funding for purchasing an ultra high field 900 MHz nuclear magnetic resonance (NMR) spectrometer for Cleveland Center for Structural Biology (CCSB), which is composed of Case Western Reserve University, Lemer Research Institute, and Cleveland State University. A significant portion of funding has been obtained from several agencies but additional support from NIH is essential to secure the full operation of the world-class NMR spectrometer. This instrument will enable the structural biologists in CCSB as well as those in other Ohio institutions to push the frontier of NMR technology and to extend their detailed structural studies to proteins and protein complexes that are factors of two to five larger than the present 25 kDa limit imposed by the existing lower field NMR instruments. Major users in this proposal all have well funded research programs (95 percent NIH funded) and are actively involved in the development and application of biomolecular NMR spectroscopy. The dramatically enhanced capabilities of the new instrument will allow them to use cutting-edge NMR technology to undertake a variety of challenging structural studies involving large cellular signaling protein complexes, protein-nucleic acid recognition, membrane proteins/receptors, protein folding/misfolding intermediates, and multi-subunit assemblies. Virtually all of the major NMR investigators, especially those in CCSB, have recently been traveling to other cities and states to gain access to ultrahigh field NMR instrumentation. Acquisition of this instrument will not only afford NMR spectroscopic access to important new classes of macromolecules and complexes but also attract top-notch faculty, students and post-docs to the area of structural biology. The new instrument will play a direct role in training graduate students and postdoctoral fellows. It will not only make significant impact on research projects of regional structural biology community but also create a cadre of NMR structural biology experts trained by the most advanced techniques. In turn, this will increase the critical mass of expertise in the region, which will promote the development of cutting edge biological research and associated high technology industry in the mid-west.